Effects of gabapentin on release of gamma-aminobutyric acid from slices of rat neostriatum.

The gamma-aminobutyric acid (GABA) analogue gabapentin (CAS 60142-96-3) has a strong anticonvulsant activity in patients, but its mechanism of action is unknown. In the present study, the effect of gabapentin was tested on the release of [3H]GABA from neostriatal slices incubated in vitro. Gabapentin displayed a bell-shaped concentration-response curve. When used at the therapeutically relevant concentration of 1 mumol/l, it nearly doubled the release of [3H]GABA, while it was without effects at concentrations of 0.1 and 10 mumol/l, respectively. The enhancing effect was blocked by the GABAA receptor antagonists picrotoxin (5 mumol/l) and bicucullin (100 mumol/l). When the slices were pre-incubated with the agonist muscimol (1 mumol/l) to occupy the GABAA receptors, 1 mumol/l gabapentin no longer enhanced the release of [3H]GABA. It is concluded that gabapentin can enhance the release of [3H]GABA, when used at a therapeutically relevant concentration. GABAA receptors are involved in this effect which may contribute to the agent's anticonvulsant activity.